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HDAC3:SMRT Fluorescent Probe 2-FAM-InsP5 Small Molecule (Tool Compound)

Invented by Dr Andrew Riley at University of Oxford, Prof Barry Potter at University of Oxford

Info

Catalogue Number 153334
Antigen/Gene or Protein Targets HDAC3:SMRT Complex
Synonyms HDACs; Histone deacetylases; SMRT; silencing mediator for retinoid or thyroid-hormone receptors; Nuclear receptor co-repressor 2; NCOR2; HDAC:SMRT3; 2-FAM-InsP5; T3 receptor-associating cofactor 1; TRAC-1
Type Fluorescent Probe
Relevance Class I histone deacetylase (HDAC) enzymes are involved in epigenetic gene regulation by controlling acetylation of lysine sidechains in histone tails They form a catalytic subunit for other large protein complexes that repress gene expression when targeted to genomic DNA. The Class I HDAC family includes HDACs 1, 2, 3 & 8, however only HDAC3 is recruited exclusively to the SMRT co-repressor complex.

Functional and structural studies of HDACs when bound to their cognate corepressors has revealed that the regulation of their activity is controlled intracellularly by inositol phosphates. The molecule, Ins(1,4,5,6)P4, had been found to locate in the binding pocket formed between HDAC3 and SMRT.

The transcriptional coregulatory protein SMRT contains several nuclear receptor-interacting domains possessing modulatory functions including several autonomous repression domains. SMRT functions as a repressive coregulatory factor (corepressor) for many transcription factor pathways. SMRT also functions as a platform, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors. Targeting HDACS provides promising epigenetic therapies for many diseases including Alzheimer’s and spinal muscular atrophy.
Molecular Formula C29H32NO27P5.4.5Et3N
lUPAC 2-O-(2-(5-fluoresceinylcarboxy)-aminoethyl)-myo-inositol 1,3,4,5,6-pentakisphosphate triethylammonium salt
Molecular Weight (g/mol) 1436 g/mol
In vitro applications 2-FAM-InsP5 [2-FAM-Ins(1,3,4,5,6)P5] is a fluorescent derivative of Ins(1,3,4,5,6)P5. 2-FAM-InsP5 activates the HDAC3:SMRT complex in a similar manner to the natural ligand, Ins(1,4,5,6)P4. The binding constant (Kd) for binding of 2-FAM-InsP5 to HDAC3:SMRT measured by a direct binding assay, 0.3 ± 0.01 μM, was approximately 10-fold lower than the Kdapp for activation of the catalytic activity of HDAC3:SMRT by Ins(1,4,5,6)P4. Utility of 2_FAM-InsP5 as a tool for study of inositol phosphate kinases.
Research Area Cancer, Epigenetics & Nuclear Signalling, Gene Expression
Storage -20ºC, protect from light

References

There are 4 reference entries for this reagent.

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References: 4 entries

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase. Whitfield et al. 2018. J Med Chem. 61(19):8838-8846. PMID: 30160967.

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase.

Europe PMC ID: 30160967

Watson et al. 2016. Nat Commun. 7:11262. PMID: 27109927.

Insights into the activation mechanism of class I HDAC complexes by inositol phosphates.

Europe PMC ID: 27109927


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References: 4 entries

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase. Whitfield et al. 2018. J Med Chem. 61(19):8838-8846. PMID: 30160967.

A Fluorescent Probe Identifies Active Site Ligands of Inositol Pentakisphosphate 2-Kinase.

Watson et al. 2016. Nat Commun. 7:11262. PMID: 27109927.

Insights into the activation mechanism of class I HDAC complexes by inositol phosphates.


Add a reference